1. Field of the Invention
The present invention concerns methods and compositions for inhibiting angiogenesis, particularly pathologic angiogenesis and/or growth and metastasis of tumors. In particular embodiments, the compositions and methods concern inhibitors targeted to placenta growth factor-2 (PlGF) and/or its receptor, Flt-1, including but not limited to peptides, antibodies, antibody fragments, humanized antibodies, chimeric antibodies, antibody analogs, aptamers, organic compounds and/or any other molecule or compound known in the art that may be used to inhibit PlGF-mediated angiogenesis and/or metastasis. In more particular embodiments, the inhibitors may be peptides isolated by phage display against PlGF.
2. Description of Related Art
The high expression of angiogenic growth factors is necessary for the growth and development of diverse cancers (Cao et al., 1998, J Clin Invest 101:1055-1063). Among such angiogenic growth factors, high expression of vascular endothelial growth factor (VEGF) has received the most attention with regard to being associated with increased malignancy and metastasis (Abdulrauf et al., 1998, J Neurosurg 88:513-52; Ahmed et al., 2000, Placenta 21 Suppl A, S16-24). However, the role of VEGF and other members of the VEGF family of growth factors in tumor recurrence or metastatic growth has not been clearly established. Many treatments, including radiation, cytokines, and cytotoxic agents, owe some of their therapeutic activity to anti-angiogenic mechanisms, one of which is the down-regulation of VEGF (Taylor et al., 2002a, Clin Cancer Res 8:1213-1222; Jiang et al., 1999, Mol Carcinog 26:213-225; Machein et al., 1999, Neuropathol Appl Neurobiol 25:104-112). Yet, marked inhibition of VEGF does not always result in durable responses or even cure. This suggests that factors other than VEGF may be capable of restoring a blood supply to surviving tumor cells.
A need exists in the field for methods and compositions directed towards the effective inhibition of tumor angiogenesis and/or growth and metastasis, as well as angiogenesis associated with other diseases.